{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:16:08Z","timestamp":1791821768965,"version":"4.3.4"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,1,29]],"date-time":"2016-01-29T00:00:00Z","timestamp":1454025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,1,29]],"date-time":"2016-01-29T00:00:00Z","timestamp":1454025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Urate transporter 1 (<jats:italic>URAT1\/SLC22A12<\/jats:italic>), a urate transporter gene, is a causative gene for renal hypouricemia type 1. Among several reported nonsynonymous <jats:italic>URAT1<\/jats:italic> variants, R90H (rs121907896) and W258X (rs121907892) are frequent causative mutations for renal hypouricemia. However, no case-control study has evaluated the relationship between gout and these two variants. Additionally, the effect size of these two variants on serum uric acid (SUA) levels remains to be clarified. Here, 1,993 primary gout patients and 4,902 health examination participants (3,305 males and 1,597 females) were genotyped with R90H and W258X. These <jats:italic>URAT1<\/jats:italic> variants were not observed in any gout cases, while 174 subjects had the <jats:italic>URAT1<\/jats:italic> variant in 2,499 health examination participants, respectively (<jats:italic>P<\/jats:italic>\u2009=\u20098.3\u2009\u00d7\u200910<jats:sup>\u221246<\/jats:sup>). Moreover, in 4,902 health examination participants, the <jats:italic>URAT1<\/jats:italic> nonfunctional variants significantly reduce the risk of hyperuricemia (<jats:italic>P<\/jats:italic>\u2009=\u20096.7\u2009\u00d7\u200910<jats:sup>\u221219<\/jats:sup>; risk ratio\u2009=\u20090.036 in males). Males, having 1 or 2 nonfunctional variants of <jats:italic>URAT1<\/jats:italic>, show a marked decrease of 2.19 or 5.42\u2009mg\/dl SUA, respectively. Similarly, females, having 1 or 2 nonfunctional variants, also evidence a decrease of 1.08 or 3.89\u2009mg\/dl SUA, respectively. We show that <jats:italic>URAT1<\/jats:italic> nonfunctional variants are protective genetic factors for gout\/hyperuricemia and also demonstrated the sex-dependent effect size of these <jats:italic>URAT1<\/jats:italic> variants on SUA (<jats:italic>P<\/jats:italic> for interaction\u2009=\u20091.5\u2009\u00d7\u200910<jats:sup>\u221212<\/jats:sup>).<\/jats:p>","DOI":"10.1038\/srep20148","type":"journal-article","created":{"date-parts":[[2016,1,29]],"date-time":"2016-01-29T09:50:51Z","timestamp":1454061051000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["The effects of URAT1\/SLC22A12 nonfunctional variants,R90H and W258X, on serum uric acid levels and gout\/hyperuricemia progression"],"prefix":"10.1038","volume":"6","author":[{"given":"Masayuki","family":"Sakiyama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Matsuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiko","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiyoshi","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihide","family":"Higashino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Naito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shino","family":"Suma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asahi","family":"Hishida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Satoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Sakurai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tappei","family":"Takada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimiyoshi","family":"Ichida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ooyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nariyoshi","family":"Shinomiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,1,29]]},"reference":[{"key":"BFsrep20148_CR1","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1056\/NEJMra0800885","volume":"359","author":"DI Feig","year":"2008","unstructured":"Feig, D. I., Kang, D. H. & Johnson, R. J. Uric acid and cardiovascular risk. N. Engl. J. Med. 359, 1811\u20131821 (2008).","journal-title":"N. Engl. J. Med."},{"key":"BFsrep20148_CR2","doi-asserted-by":"publisher","first-page":"1953","DOI":"10.1016\/S0140-6736(08)61343-4","volume":"372","author":"A Dehghan","year":"2008","unstructured":"Dehghan, A. et al. Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. Lancet. 372, 1953\u20131961 (2008).","journal-title":"Lancet."},{"key":"BFsrep20148_CR3","doi-asserted-by":"publisher","first-page":"10338","DOI":"10.1073\/pnas.0901249106","volume":"106","author":"OM Woodward","year":"2009","unstructured":"Woodward, O. M. et al. Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout. Proc. Natl. Acad. Sci. USA. 106, 10338\u201310342 (2009).","journal-title":"Proc. Natl. Acad. Sci. 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The other authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20148"}}